Thermal Stability of Pharmaceuticals: Eudragit® • NETZSCH

How to Measure the Thermal Stability of Eudragit®

Standard ASTM E2550-11 describes the method of measuring the thermal stability of materials by means of thermogravimetry. As an example, let us determine the thermal stability of Eudragit^® L100-55 (Evonik Industries). To this end, you need a thermobalance to measure the mass loss of your sample during heating until thermal decomposition. The TGA measurement was carried out using the following instrument and parameters:

Instrument: NETZSCH TG 209 F1 Libra thermobalance coupled to the FT-IR System by Bruker Optics
Sample: Eudragit^® L100-55 (Evonik Industries)
Sample mass: 7.33 mg
Crucible: open aluminum oxide
Temperature program: Heating to 600°C at 10 K/min
Atmosphere: N₂ (40 ml/min)

Thermal Stability With TG-FT-IR Measurements

Figure 1 depicts the mass changes of Eudragit^® L100-55 between 40°C and 600°C. The first mass-loss step of 0.8% up to 100°C indicates the release of surface water.

Fig. 1. Mass changes of Eudragit® L100-55 during heating to 600°C. The curve Shows that the substance is thermal stable up to 185°C. — Fig. 1. Mass changes of Eudragit^® L100-55 during heating to 600°C. The curve shows that the substance is thermally stable up to 185°C.

Water release or decomposition start?

The second mass loss of 5.9% at 200°C (DTG peak) is associated with the release of:

Crystal water;
CH₂ and CH₃ molecules (bands in the range 3000-2800 cm^–1 and above 1000 cm^–1).

(see FT-IR spectrum of the gases released at 206°C in figure 2) In this case, coupling to the FT-IR System is really important: detection of the CH₂ and CH₃ molecules in the released gases proves that the mass loss is not only due to the release of water! The Eudragit^® sample begins to decompose during this mass-loss step starting at 185°C! This temperatureof decomposition is related to the thermal stability of the sample.

Fig. 2. FT-IR spectrum of the gases released at 206°C. It indicates that the mass-loss step beginning at 185°C is due to decomposition. Thus, the sample is thermally stable up to 185°C.

The Decomposition Goes On…

The peak at 294°C in the DTG curve is associated with yet another step in the decomposition process: the release of carbon dioxide and probably ethanol (figures 3 and 4). This can be explained by the splitting of an ester group off the Eudragit^® molecule.

Fig. 3. Comparison of the FT-IR spectrum of the gases released at 295°C (top) with the EPA-NIST-FT-IR spectrum of carbon dioxide (bottom)

Fig. 3. Comparison of the FT-IR spectrum of the gases released at 295°C (top) with the FT-IR spectrum of ethanol (bottom [4]) — Fig. 4. Comparison of the FT-IR spectrum of the gases released at 295°C (top) with the FT-IR spectrum of ethanol (bottom)

The last and main decomposition step, with a mass loss of 88.5%, occurs at 393°C (DTG peak temperature). The characteristic bands of:

ethanol
carbon dioxide
carbon monoxide (2300 cm^-1 to 2100 cm^-1)
ester substance (band at 1749 cm^-1)
parts of the carbon Backbone (bands at 1460 cm^-1 and 1380 cm^-1)

are detected in the FT-IR-spectrum of the gases released at 393°C (figure 5). It suggests that the ester part C₂H₅-O-CO-CxHy breaks off from the molecule.

Conclusion

Under the selected conditions (inert atmosphere, heating rate of 10 K/min), the investigated Eudragit^® sample starts to decompose at 185°C (onset temperature of the TGA curve). The fact that this is really the start of decomposition is revealed by the occurrence of C-H bonds in addition to crystal water.